EP2451500B1 - Simplified peritoneal equilibration test for peritoneal dialysis - Google Patents

Simplified peritoneal equilibration test for peritoneal dialysis Download PDF

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EP2451500B1
EP2451500B1 EP10726372.5A EP10726372A EP2451500B1 EP 2451500 B1 EP2451500 B1 EP 2451500B1 EP 10726372 A EP10726372 A EP 10726372A EP 2451500 B1 EP2451500 B1 EP 2451500B1
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Prior art keywords
substance
patient
dialysis
concentration
dialysis fluid
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French (fr)
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EP2451500A1 (en
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Ying-Cheng Lo
Alp Akonur
Sarah Stobo Prichard
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Baxter Healthcare SA
Baxter International Inc
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Baxter International Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1601—Control or regulation
    • A61M1/1619—Sampled collection of used dialysate, i.e. obviating the need for recovery of whole dialysate quantity for post-dialysis analysis

Definitions

  • the present disclosure relates generally to medical fluid delivery systems and methods. More particularly, this disclosure includes systems, methods and apparatuses for administering a simplified peritoneal equilibration test.
  • the test will more easily help the patient and caregivers to determine whether a patient will benefit from peritoneal dialysis.
  • the test is also useful for helping to determine particular optimal therapies that may be administered to the patient.
  • kidney failure causes several physiological impairments and difficulties. The balance of water, minerals and the excretion of daily metabolic load is no longer possible and toxic end products of nitrogen metabolism (urea, creatinine, uric acid, and others) can accumulate in blood and tissue. Kidney failure and reduced kidney function have been treated with dialysis. Dialysis removes waste, toxins and excess water from the body that would otherwise have been removed by normal functioning kidneys. Dialysis treatment for replacement of kidney functions is critical to many people because the treatment is life saving.
  • Hemodialysis and peritoneal dialysis are two types of dialysis therapies used commonly to treat loss of kidney function.
  • a hemodialysis (“HD") treatment utilizes the patient's blood to remove waste, toxins and excess water from the patient.
  • the patient is connected to a hemodialysis machine and the patient's blood is pumped through the machine.
  • Catheters are inserted into the patient's veins and arteries so that blood can flow to and from the hemodialysis machine.
  • the blood passes through a dialyzer of the machine, which removes waste, toxins and excess water from the blood.
  • the cleaned blood is returned to the patient.
  • a large amount of dialysate for example about 120 liters, is consumed to dialyze the blood during a single hemodialysis therapy.
  • Hemodialysis treatment lasts several hours and is generally performed in a treatment center about three or four times per week.
  • HF hemofiltration
  • substitution or replacement fluid to the extracorporeal circuit during treatment (typically ten to ninety liters of such fluid). That substitution fluid and the fluid accumulated by the patient in between treatments is ultrafiltered over the course of the HF treatment, providing a convective transport mechanism that is particularly beneficial in removing middle and large molecules.
  • HDF Hemodiafiltration
  • hemodiafiltration is another blood treatment modality that combines convective and diffusive clearances.
  • HDF uses dialysate to flow through a dialyzer, similar to standard hemodialysis, providing diffusive clearance.
  • substitution solution is provided directly to the extracorporeal circuit, providing convective clearance.
  • Peritoneal dialysis uses a dialysis solution, also called dialysate, which is infused into a patient's peritoneal cavity via a catheter.
  • the dialysate contacts the peritoneal membrane of the peritoneal cavity. Waste, toxins and excess water pass from the patient's bloodstream, through the peritoneal membrane and into the dialysate due to diffusion and osmosis, i.e., an osmotic gradient occurs across the membrane.
  • the spent dialysate is drained from the patient, removing waste, toxins and excess water from the patient. This cycle is repeated.
  • Peritoneal dialysis machines are used to accomplish this task. Such machines are described, for example, in the following U.S. Patents: 5,350,357 ; 5,324,422 ; 5,421,823 ; 5,431,626 ; 5,438,510 ; 5,474,683 ; 5,628,908 ; 5,634,896 ; 5,938,634 ; 5,989,423 ; 7,153,286 ; and 7,208,092 .
  • CAPD continuous ambulatory peritoneal dialysis
  • APD automated peritoneal dialysis
  • CFPD continuous flow peritoneal dialysis
  • CAPD is a manual dialysis treatment.
  • the patient manually connects an implanted catheter to a drain, allowing spent dialysate fluid to drain from the peritoneal cavity.
  • the patient then connects the catheter to a bag of fresh dialysate, infusing fresh dialysate through the catheter and into the patient.
  • the patient disconnects the catheter from the fresh dialysate bag and allows the dialysate to dwell within the peritoneal cavity, wherein the transfer of waste, toxins and excess water takes place.
  • APD Automated peritoneal dialysis
  • CAPD Automated peritoneal dialysis
  • APD machines perform the cycles automatically, typically while the patient sleeps.
  • APD machines free patients from having to manually perform the treatment cycles and from having to transport supplies during the day.
  • APD machines connect fluidly to an implanted catheter, to a source or bag of fresh dialysate and to a fluid drain.
  • APD machines pump fresh dialysate from a dialysate source, through the catheter, into the patient's peritoneal cavity, and allow the dialysate to dwell within the cavity, and allow the transfer of waste, toxins and excess water to take place.
  • the source can be multiple sterile dialysate solution bags.
  • APD machines pump spent dialysate from the peritoneal cavity, though the catheter, to the drain. As with the manual process, several drain, fill and dwell cycles occur during APD. A "last fill” occurs at the end of CAPD and APD, which remains in the peritoneal cavity of the patient until the next treatment.
  • Both CAPD and APD are batch type systems that send spent dialysis fluid to a drain.
  • Tidal flow systems are modified batch systems. With tidal flow, instead of removing all of the fluid from the patient over a longer period of time, a portion of the fluid is removed and replaced after smaller increments of time.
  • Continuous flow, or CFPD, systems clean or regenerate spent dialysate instead of discarding it.
  • These systems pump fluid into and out of the patient, through a loop.
  • Dialysate flows into the peritoneal cavity through one catheter lumen and out another catheter lumen.
  • the fluid exiting the patient passes through a reconstitution device that removes waste from the dialysate, e.g., via a urea removal column that employs urease to enzymatically convert urea into ammonia.
  • the ammonia is then removed from the dialysate by adsorption prior to reintroduction of the dialysate into the peritoneal cavity. Additional sensors are employed to monitor the removal of ammonia.
  • CFPD systems are typically more complicated than batch systems.
  • ultrafiltration is the process by which water (with electrolytes and other neutral solutes) moves across a membrane, such as a dialyzer or peritoneal membrane.
  • ultrafiltration in peritoneal dialysis is a result of osmotic and hydrostatic pressure differences between blood and dialysate across the patient's peritoneal membrane.
  • concentration of metabolic substances in the patient's bloodstream such as urea concentration, ⁇ 2 -microglobulin, creatinine concentration, and so forth.
  • Each patient is different, possessing for instance, a unique peritoneal membrane, its own separation characteristics, and its unique response to peritoneal dialysis.
  • Each patient is also different with respect to body surface area (BSA) and total body water volume, which also have an effect on transport characteristics.
  • BSA body surface area
  • Each patient is different in terms of transport characteristics that relate to the ultrafiltration rate.
  • Each patient is also different in terms of response to dialysis, that is, the amount of water and waste removed in a given time period, using a given fill volume, a particular dialysis fluid, and so forth.
  • a peritoneal equilibration test determines the relative rate of transmembrane transport. Patients can then be classified as high-rate transporters, high-average transporters, low-average transporters, or low-rate transporters, depending on the speed of waste removal and the speed of absorption of glucose from the dialysis fluid. Other peritoneal membrane transport categories or classes may also be used, such as high, average, and low transporters. Patients may also be classified in terms of their total body surface area (BSA), which depends only on the patient's height and weight.
  • BSA total body surface area
  • the rate of water removal is different from the rate of waste removal, and both depend on the patient transporter type and is indirectly related to the patient membrane transport type.
  • fast transporters can quickly pass metabolic waste, but glucose from the dialysis solution is rapidly absorbed into the body.
  • glucose concentration in the dialysate decreases and the osmotic gradient or driving force diminishes within a variable period of time, depending on the patient transporter type.
  • high transporters may benefit more from short dwell times, such as those used in automated peritoneal dialysis (APD), where the effect of high osmotic gradients is still present.
  • API automated peritoneal dialysis
  • the osmotic gradient will be sustained for a longer period of time in the case of a low transporter patient, resulting in a larger volume of ultrafiltrate removal.
  • a patient will likely benefit from a longer dwell time, such as a continuous ambulatory peritoneal dialysis (CAPD) and with perhaps only a single nighttime exchange.
  • CAPD continuous ambulatory peritoneal dialysis
  • Much useful information about a patient's response to therapy can be learned from administering the PET to the patient. The results of the PET can then be used to administer the therapy that would lead to the best outcome for that patient.
  • present PET tests also require a blood test.
  • the difficulty in administering the PET may be a significant barrier in determining the therapy best suited for a patient. This is because the present PET requires the patient to visit a dialysis center, requires a nurse's time as well as the patient's time to obtain a blood sample, and causes discomfort to the patient.
  • JP 2000-271127 discloses a system and method for evaluating the function of a patient peritoneum.
  • One embodiment of the present disclosure is system for performing a simplified peritoneal equilibration test ("S-PET").
  • the software program is programmed to use the formula to calculate the equilibrium concentration of the substance, wherein the equilibrium concentration of the substance in the dialysis fluid is approximately equal to an equilibrium concentration of the substance in the patient's blood.
  • the software is further programmed to suggest at least one transport property of the peritoneum of the patient.
  • the software is programmed to suggest whether the peritoneum of the patient has a transport property selected from the group consisting of: a high transporter property, a high-average transporter property, a low-average transporter property, and a low transporter property.
  • the software program is programmed to use the formula to calculate the equilibrium concentration of the substance and the equilibration time constant of the substance using the inputs and to suggest whether the peritoneum of the patient has a membrane transporter property selected from the group consisting of: a high transporter property, a high-average transporter property, a low-average transporter property, and a low transporter property.
  • a further embodiment of the present disclosure is a method for performing a simplified peritoneal equilibration test.
  • the method includes steps of taking at least two samples of dialysis fluid after a start of a dialysis therapy, the samples taken at least two separate times, and analyzing the dialysis fluid samples only for concentrations of a substance in the dialysis fluid.
  • a method also includes a step of selecting a category of a membrane transporter property from among the known categories.
  • Also disclosed is a method for performing a simplified peritoneal equilibration test that includes steps of administering a peritoneal dialysis therapy to a patient, including taking at least two samples of dialysis fluid after a start of the dialysis therapy, the samples taken at times separated by at least about an hour.
  • the method also includes a step of selecting a category of a membrane transporter property.
  • Embodiments of the present disclosure have an advantage in that a reasonable approximation of a patient's membrane transport properties is available with as few as two or three samples of dialysate fluid. Another advantage is that it is possible to classify the patient's membrane transport properties with this more convenient test. Another advantage is that a blood sample, and subsequent analysis of the blood sample, is not required. Thus, it is possible to carry out the S-PET at home or other location where it is not convenient to obtain a blood sample or to obtain an analysis of the blood sample.
  • Fig. 1 is a prior art depiction of patient membrane categories.
  • Fig. 2 is a graph of how the prior art fails to adequately place patients among the categories
  • Figs. 3A to 3D are charts depicting how the simplified PET test uses data points to categorize patients among the categories.
  • Fig. 4 is a flow chart depicting the classifying method disclosed herein.
  • the graph also presents on the ordinate or y-axis the ratio of the concentration of creatinine in the used dialysate to the concentration of creatinine in blood plasma, the ratio D/P, that is, in the concentration in the spent dialysis fluid to the concentration in the patient's blood plasma.
  • Dialysis patients may be classified by the transport characteristics of their peritoneal membrane into one of four categories, as shown in Fig. 1 .
  • "High” or “H” transporters have a higher ratio of a concentration of the waste-product solute in the dialysate fluid to that in their blood, and a lower ratio of glucose in the dialysis fluid to the initial concentration of glucose in the dialysis fluid, when compared to "low” or “L” transporters.
  • Patients with intermediate transport characteristics may be classified as “high-average” or "HA” transporters, or "low-average” or “LA” transporters.
  • a therapy should involve greater amounts of dialysis fluid and shorter dwell times for higher ultrafiltrate.
  • lesser amounts of dialysis fluid may be combined with longer dwell times to achieve both higher ultrafiltrate and more solute removal.
  • Fig. 1 is a summary chart that leaves off much of the details in how these charts were prepared. As is well known to those with ordinary skill in the art, these charts are actually first constructed as time-scales, with time plotted on the abscissa and D/D 0 or D/P plotted on the ordinate. See Zyblut 1987. The ratio of D/D 0 and D/P may then be plotted, leaving out the time element. The result is an elegant solution that appears to neatly categorize patients.
  • a standard PET test may involve an entire eight to twelve hour night exchange with 3.86% or 2.27% glucose solution preceding the test exchange, if the test includes a kinetic analysis of the patient, which is not strictly necessary to determine the patient's membrane transport category.
  • One technique is to then drain the abdomen completely over a twenty-minute period, and then infuse about two liters of 2.27% glucose over a ten-minute period.
  • the patient is turned side to side and 200 ml is drained immediately after infusion, including a ten-ml sample for glucose, urea and creatinine.
  • the remaining 190 ml is then returned for the dwell and this sampling procedure is repeated at several intervals, such as 30 minutes, one hour, two hours and three hours, each with a drain and a subsequent two-liter infusion.
  • a blood sample is also taken for tests for blood urea nitrogen ("BUN") and creatinine.
  • BUN blood urea nitrogen
  • a final infusion and dwell is taken at the four-hour mark, followed by a drain and a measurement of total effluent volume.
  • the D/d 0 glucose and D/P creatinine results are used in a chart similar to those described above to classify the patient's peritoneal membrane in one of the four categories. This procedure is labor-intensive and very intrusive on the patient because of the number of samples needed, including a blood sample.
  • Adcock et al. suggested a faster method in which the initial glucose concentration and other intermediate samples were not measured, and used only the plasma sample and the last, four-hour time point.
  • Adcock et al. Clinical Experience and Comparative Analysis of the Standard and Fast Peritoneal Equilibration Tests (PET), Advances in Peritoneal Dialysis, vol. 8, pp. 59-61 (1992 ).
  • La Milia suggested a method in which the standard four-hour dwell is replaced with a one hour dwell using a 3.86% glucose solution, but still required the blood sample.
  • La Milia et al. Mini Peritoneal Equilibration Test: A simple and fast method to assess free water and small solute transport across the peritoneal membrane, Kidney Int'l 68, pp. 840-846 (2005 ).
  • Fig. 2 depicts the results of the survey for both the D/P and the D/D 0 axes. These data depict results using a standard PET as described above. Approximately 40% of the patients thus do not fit into any of the four categories. Another way of saying this is that the long and involved PET procedure described above does not correctly classify about half of all patients. It is expected that the shorter PETs discussed above will also misclassify or fail to classify at least about that percentage of patients.
  • the present disclosure describes a new test, the S-PET, that is less labor intensive and uses what may be described as more effective sampling.
  • a peritoneal dialysis machine such as a HomeChoice® dialysis machine, is helpful in administering the test.
  • samples of the dialysis fluid are taken for analysis of urea, creatinine and glucose content.
  • No blood sample is taken and either 2.27% glucose (DianealTM 2.27%) or 3.86% glucose (DiancalTM 3.86%) dialysis solution may be used. Measurements may be taken initially, at thirty minutes and at the one, two and four hour marks. Based on these tests, an estimate for a curve-fit is made for a final creatinine concentration in the dialysis fluid.
  • Tests may instead be based on only two or three readings, such as readings at four hours and eight hours, for example, or tests taken at one hour, two hours and eight hours.
  • the reading at the start of the test may be taken as zero, for example, to spare the patient the discomfort and labor in taking what is likely the least-useful test.
  • other time points may be used.
  • Figs. 3A to 3D depict graphically the result of tests for creatinine for the four categories of patients, including a blood sample.
  • Each of the graphs displays creatinine concentration test results plotted against the time period after infusion of the dialysis fluid.
  • Each graph also marks a plasma creatinine concentration taken at about two hours.
  • the final point in each graph is an estimate of the equilibrium creatinine concentration for the patient using a standard curve-fitting program, such as ExcelTM from Microsoft Corp., Redmond, WA, U.S.A. or MatLabTM from The MathWorks Inc., Natick, MA, U.S.A.
  • the dialysis fluid for a typical high transporter patient is seen to have a rapidly-growing concentration of creatinine.
  • the creatinine concentration reaches a maximum after about 4 to 5 hours. There is thus no benefit in creatinine removal after a dwell period of about 4 to 5 hours.
  • the test result is achieved simply by infusing the patient and then removing a 10 ml sample at the intervals for which the dots are shown, at the test beginning and after 2 hours and 4 hours.
  • a curve fit is then used to estimate a final or equilibrium concentration for the solute that would be achieved in a very long dwell time.
  • a computer is useful in finding a curve fit for the data. As seen in Fig. 3A , the curve fit is excellent and a final estimate of about 8 mg/dL is very close to the four-hour measurement of about 7.5 mg/dL.
  • a blood plasma sample was also taken at about the 2-hour mark for confirmation.
  • the blood plasma sample for the high-transporter patient had a plasma creatinine concentration of about 8.5 mg/dL at the 2-hour point.
  • the plasma concentration samples taken and displayed at Figs. 3A to 3D confirm that the plasma concentration is inversely related to membrane transport speed, as expected. That is, as creatinine clearance decreases, more creatinine remains in the patient's blood plasma.
  • Fig. 3B A similar result is seen in Fig. 3B , for patients who may be categorized as high-average transporters, that is, patients whose peritoneal membranes are somewhat less permeable than those of the high transporters.
  • the equilibrium concentration of creatinine is estimated at the end of the curve in Fig. 3B at about 7 mg/dL, which is very close to the 4-hour sample concentration of about 6.5 mg/dL.
  • a blood plasma sample showed a creatinine concentration of about 9 mg/dL, a little higher than the high transporter patients, indicating that less creatinine was removed from these patients than from the high transporter patients.
  • Fig. 3C depicts results for patients with peritoneal membranes that may be categorized as low-average transporters. Creatinine concentration in the 4-hour sample was about 6 mg/dL, a little lower than that shown for the high-average transporters. However, the estimate for the equilibrium creatinine concentration was about 7 mg/dL, very close to that for the high-average transporters. The blood plasma sample shows significantly more creatinine, about 11 mg/dL, compared to high and high-average transporters.
  • Fig. 3D depicts results for low-transporter patients, that is, those patients whose peritoneal membranes are least amenable to mass transfer.
  • Fig. 3D depicts, there is no rapid rise in creatinine concentration in the first four hours, compared with the other three categories of transporters. However, the concentration continues to rise over a longer period of time, with an eventual final estimate for the equilibrium concentration of about 7.5 mg/dL, which is close to low-average and high-average transporters.
  • the blood plasma creatinine level at the two-hour mark was about 11 mg/dL, similar to low-average transporters, and significantly higher than patients with membranes classed as either high or high-average.
  • patients with peritoneal membranes classed as high or high-average are seen to have lower creatinine levels after two hours of dialysis than patients with low or low-average peritoneal membranes.
  • Figs. 3A to 3D depict the rise of creatinine levels in spent dialysis fluid. If urea were used as the solute of interest, a similar series of curves would result, but with less noticeable differences between the curves because of the faster transport of the small urea molecules across the peritoneal membrane.
  • glucose in the dialysis fluid would be expected to decrease, as the glucose is transported from the dialysis fluid across the peritoneal membrane and infuses into the blood of the patient.
  • High transporters would be expected to see a rapid infusion of glucose, while low transporters would expect a slower infusion. Since glucose is the osmotic agent in the dialysis fluid, the loss of glucose from the dialysis fluid lowers its effectiveness in providing the driving force for ultrafiltration.
  • CD t - CD eq CD 0 - CD eq e - t / ⁇
  • CD t is a concentration of the at least one substance at one of the separate times at which dialysis fluid samples are taken
  • CD eq is an equilibrium concentration of the at least one substance
  • CD 0 is an initial concentration of the at least one substance
  • t is one of the separate times
  • ⁇ is an equilibration time constant that is representative of a transport property of a peritoneum of the patient.
  • CD eq and ⁇ may be estimated using this equation and a curve fit program, based on the measured solute concentrations in the samples taken.
  • CD eq is an equilibrium concentration of the substance in the dialysis fluid and is approximately equal to a concentration of the substance in the patient's blood at equilbrium, that is, after a long period of time.
  • the equilibration time constant for the four categories of transporters were found to be, respectively, 107 minutes, 175 minutes, 242 minutes and 406 minutes, for creatinine for high, high-average, low-average and low transporters, respectively.
  • clinical studies with large number of patients should be conducted. Time constants for glucose and urea are expected to be different.
  • the formula is made part of a computer software program, which is entered into a computer memory or placed onto a medium accessible to a computer for performing calculations necessary to derive the CD eq of the substance for the particular patient.
  • test results may be analyzed and graphed in a variety of ways to increase their utility and also to increase the confidence that the new labor-saving test procedure can be used rather than the more arduous traditional PET.
  • the ability to predict the equilibrium levels in the dialysis fluid means that the equivalent levels of plasma urea and creatinine are not needed. These correlations may be used with confidence and the labor saved makes the procedure easier for both patients and caregivers. Additional data points may be used in the above formula if the information is available from additional samples of dialysate from the patient.
  • test may be performed at a hospital, an out-patient clinic, or even at home. This may be useful, for example, as an update if a patient or a caregiver has reason to suspect that the transport properties of the membrane of the patient have changed.
  • test results the patient or a caregiver may alert a physician to the change and suggest that a change in prescription may be appropriate.
  • the physician or caregiver may use the test results to compare to previous test results, if any, and see whether there has indeed been a change in test results for the patient of interest.
  • test results may be used in conjunction with suitable software, such as PDAdequest® or RenalSoftTM from Baxter International Inc., Deerfield, IL, USA. This software may then be used by the physician to update a prescription for the patient.
  • kits for analyzing the test results may include smaller, substance-specific instruments, test strips, cuvettes for dialysis fluid samples for insertion into the instruments, suitable pumps, and so on.
  • the test may be performed and samples taken using a standard peritoneal dialysis machine, such as the Baxter HomeChoice® peritoneal dialysis machine.
  • the machine is programmed to take samples at the appropriate times, such as at the start of dialysis and at two hours and four hours. In another example, samples may be taken at two hours and eight hours, or at four hours and eight hours.
  • the samples are then analyzed for the appropriate solute or solutes, such as glucose, urea or creatinine.
  • the machine is programmed as desired and the patient may already be equipped with a kit or a disposable that includes the necessary tools to detect or measure the appropriate solute. These tools may include chemical reagents, test strips, optical components, conductivity cells, pH cells, and the like.
  • a microfluidic chemical analyzer system can be used to detect the concentration of the substance, i.e. creatinine, urea, and glucose, in the dialysate.
  • the microfluidic system may consist of small-scale channels, pumps, and detection systems. Microfluidic channels may be chemically treated to alter material surface properties in order to achieve preferred surface tension characteristics to induce motion of the dialysate, i.e. passive pumping. Alternatively, an active micro pump can be used to move the dialysate within the microfluidic analyzer. Using this motion, micro-volume dialysate samples can be obtained and routed to the detector for the appropriate analysis. The same technique, or a variety of techniques, i.e.
  • microfluidic analyzer may or may not be a part of the disposable set used by the patient for the dialysis therapy.
  • Microfluidic disposable systems are available from, for example, Weidmann Plastics Technology, AG, Rapperswil-Jona, Switzerland, and ThinXXS Microtechnology AG, of Zweibrucken, Germany.
  • test strips and a readout may be used for glucose and creatinine.
  • Such systems are available from Polymer Systems Technology, Inc., Indianapolis, IN, USA, under the trade name of CardioChek and Bioscanner Creatinine Test Strips. Test strips are described, for example in U.S. Pat, No. 6,130,054 and U.S. Pat. Appl. Publ. 2006/0228767 . Test strips for urine are also described, for example, in U.S. Pat. No. 6,699,720 .
  • Such analytical strips, and others are typically impregnated with one or more reagents for reaction with the analyte or solute of interest.
  • these disposable, one-time-use devices may take the form of small containers or cuvettes.
  • the container or cuvette may be impregnated or coated on its inside with reagents for detecting the solute or analyte of interest.
  • a dialysis fluid sample is obtained, the sample is pumped or drained into the container.
  • the container may allow for a short residence time, if needed, and then the concentration is indicated by a color change, by the appearance of one or more lines, or other appearance change.
  • Optical methods are well known and are especially useful for testing for concentrations of urea.
  • assay kits are available, for example, from BioAssay Systems, Hayward, CA, USA.
  • Other methods well known to those with skill in analytical art include conductivity probes, pH meters, and so forth.
  • conductivity probes There are many ways to detect the solute or solutes of interest once the samples have been obtained at the prescribed or appropriate time intervals. Whether disposable or reusable, these techniques will work well at home or in environments where a sophisticated medical or chemical laboratory is not available.
  • a home device or a kit may include test strips, reagents, or measuring devices designed to capture samples of the dialysis fluid for analysis of one or more of the primary solutes of interest, e.g., creatinine, urea or glucose.
  • the dialysis machine may include a disposable accessory or a kit for capturing samples and measuring the solute of interest by one of the means discussed above.
  • a home kit for administering a simplified peritoneal equilibration test may include the necessary reagents, devices, or strips for analysis.
  • a pump for appropriate sampling of dialysis fluid may be obtained, for example, from ThinXXS Microtechnology AG, of Zweibrucken, Germany.
  • the Bimor pump is available from Nitto-Kohki Inc., of Tokyo, Japan.
  • An electro-kinctic pump is also available from Eksigcnt Technologies, Inc, of Dublin, CA, USA.
  • the improved test also may include a measure of ultrafiltrate ("UF"), that is, the amount of water crossing the pcritoneal membrane and causing an increase in the volume that is ultimately drained from the patient during dialysis.
  • UF ultrafiltrate
  • the amount of UF generated is an important determinant of patient transport status.
  • the amount of UF generated can be measured with standard APD machines, such as the balance chambers in a HomeChoiceTM peritoneal dialysis machine.
  • An integrated scale may be used instead.
  • a scale or flow measurement device may be used. Any of these measurements may be used in the S-PET to help determine the transport category of a patient, understanding that patients with high or high-average transporting membranes will tend to generate ultrafiltrate more quickly than patients with low or low-average transporting membranes
  • the methods described above may be summarized in the flow-chart of Fig. 4 or other embodiments.
  • the method of Fig. 4 is used to administer an S-PET to a patient as part of a process for administering peritoneal dialysis therapy.
  • the test involves administering 41 peritoneal dialysis therapy to the patient and also taking 42 at least two samples of dialysis fluid from the dialysis therapy at two separate times. As discussed above, the times may include an initial sample at the beginning of the therapy, followed by additional samples 2 hours and 4 hours later. Alternatively, a zero concentration may be assumed for the initial sample and two samples may be taken at later times.
  • the samples are analyzed for concentrations of an analyte of interest, such as urea, creatinine or glucose.
  • the analysis is typically conducted via a chemical, optical, colorimetric, or other accepted analytical technique.
  • more samples may be taken, and the longer the dwell time, typically, the better, because the sample gets closer to its actual equilibrium value, D eq , for the solute of interest.
  • two such samples may be taken and analyzed 43 for their creatinine concentrations.
  • the formula may also be used to calculate the time constant for the appropriate substance, which may be accomplished at the same time or independently. Note that the equation has two unknowns, the D eq and the time constant. These concentrations may then be used to calculate 44 the equilibration concentration, D eq , of creatinine, per Figs. 3A to 3D , using the equation and time constants given above.
  • Other analytical calculating techniques may be used, such as comparing the samples with previously-compiled tables or graphs of concentrations of the substance for known transporter types over periods of time. One of these analytical techniques is then used to correlate 45 the results of the analysis to known transporter properties. A selection is then made 46 of which transport category most closely matches the test results for the patient.
  • a level of creatinine in the blood plasma (P) may be known or may be estimated for a patient
  • the level of creatinine at the four hour mark, D 4 , or other time may then be used to calculate D/P, such as D 4 /P, the relative concentration of creatinine at four hours to blood level at the appropriate time.
  • a table may then be used to compare D 4 /P to known categories of transport groups, and the appropriate categorization or selection may then be made. These tables, as well as others, may also be entered into a computer memory so that the necessary calculations may be accomplished with a computer.
  • the computer may be the same computer used to operate a peritoneal dialysis machine, or may be a different computer. In general, it may not be strictly necessary to determine a patient's classification in order to prescribe an appropriate therapy. Data from a patient may be used with graphs such as those depicted in Fig. 2 to determine the appropriate therapy without necessarily determining a specific transporter category.
  • two or more samples may be taken and analyzed 43 for their glucose concentrations.
  • the concentration of glucose at the four hour mark may be divided by the initial concentration of glucose, i.e., the value of D 4 /D 0 determined 44, thus performing a mathematical operation to determine a concentration of the glucose at the four hour mark relative to the concentration of glucose at the start of the therapy.
  • the result may then be compared 45 to tables of a known group of properties using a graph such as Fig. 4 .
  • the appropriate category of membrane transport properties may then be selected 46 from among the accepted or known categories by using a graph or by using software. It is also possible to simply use the test results as inputs to a peritoneal dialysis software program, such as PD AdequestTM or RenalSoftTM, from Baxter International, Inc.
  • Additional calculations and refinements may be made during the process as additional information becomes available. For example, measurements may be made using solute levels at three different times, such as at the start of the test, and at two and four hours, and the equilibration time constant used with the equation above to estimate an initial fit and category selection. A fourth data point may then be estimated, and using the four data points, a second iteration run to refine the data and achieve a better approximation.
  • glucose levels may require special attention when dealing with diabetic patients.
  • Glucose levels in diabetic patients may not be constant and thus the transport of glucose from dialysis fluid may be highly variable depending on whether glucose levels in the patient's blood are in control, or are instead elevated or depressed out of normal ranges, e.g., 70-99 mg/dL.
  • Other waste products of interest may also be used.

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EP10726372.5A 2009-07-07 2010-06-02 Simplified peritoneal equilibration test for peritoneal dialysis Not-in-force EP2451500B1 (en)

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US12/498,847 US8180574B2 (en) 2009-07-07 2009-07-07 Simplified peritoneal equilibration test for peritoneal dialysis
PCT/US2010/037082 WO2011005387A1 (en) 2009-07-07 2010-06-02 Simplified peritoneal equilibration test for peritoneal dialysis

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EP2451500A1 (en) 2012-05-16
MX2012000388A (es) 2012-03-07
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US20110010101A1 (en) 2011-01-13
WO2011005387A1 (en) 2011-01-13
US8180574B2 (en) 2012-05-15

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